Biology subjects

Silva, R. S.

Publications and source records attributed to Silva, R. S..

3 recordsLinked to original sources

bioRxiv2026

Insulin synthesis is sustained by Tent5 poly(A) polymerases

Insulin is an essential regulator of glucose homeostasis in vertebrates, and impairment of its synthesis or action leads to diabetes with severe health complications in humans. It is therefore essential to understand how beta cells control insulin synthesis and secretion, including the transcription, translation and decay of its messenger RNA. Using sequencing-based poly(A) tail length profiling from human tissue, genetic evidence for type 2 diabetes, bulk and single-cell transcriptomics and perturbation experiments, here we find that the insulin mRNA is stabilized by the activity of noncanonical poly(A) polymerases of the Tent5 family. We show that Tent5 activity is specific, promoted by both localization at the endoplasmic reticulum and regulatory sequences within the insulin mRNA and regulated by glucose. Overall, our findings provide a mechanistic link between the dynamic control of insulin production by beta cells and the direct regulation of insulin mRNA metabolism.

molecular biology↗

bioRxiv2023

Markerless motion capture estimates of lower extremity kinematics and kinetics are comparable to marker-based across 8 movements

Motion analysis is essential for assessing in-vivo human biomechanics. Marker-based motion capture is the standard to analyze human motion, but the inherent inaccuracy and practical challenges limit its utility in large-scale and real-world applications. Markerless motion capture has shown promise to overcome these practical barriers. However, its fidelity in quantifying joint kinematics and kinetics has not been verified across multiple common human movements. In this study, we concurrently captured marker-based and markerless motion data on 10 healthy subjects performing 8 daily living and exercise movements. We calculated the correlation (Rxy) and root-mean-square difference (RMSD) between markerless and marker-based estimates of ankle dorsi-plantarflexion, knee flexion, and three-dimensional hip kinematics (angles) and kinetics (moments) during each movement. Estimates from markerless motion capture matched closely with marker-based in ankle and knee joint angles (Rxy [≥] 0.877, RMSD [≤] 5.9{degrees}) and moments (Rxy [≥] 0.934, RMSD [≤] 2.66 % height x weight). High outcome comparability means the practical benefits of markerless motion capture can simplify experiments and facilitate large-scale analyses. Hip angles and moments demonstrated more differences between the two systems (RMSD: 6.7{degrees} - 15.9{degrees} and up to 7.15 % height x weight), especially during rapid movements such as running. Markerless motion capture appears to improve the accuracy of hip-related measures, yet more research is needed for validation. We encourage the biomechanics community to continue verifying, validating, and establishing best practices for markerless motion capture, which holds exciting potential to advance collaborative biomechanical research and expand real-world assessments needed for clinical translation.

bioengineering↗

bioRxiv2017

Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus

Autosomal dominant North Carolina macular dystrophy (NCMD) is believed to represent a failure of macular development. The disorder has been assigned by linkage to two loci, MCDR1 on chromosome 6q16 and MCDR3 on chromosome 5p15-p13. Recently, noncoding variants upstream of PRDM13 and a large duplication including IRX1 have been identified. However, the underlying disease-causing mechanism remains uncertain. Through a combination of sequencing studies, we report two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16. One duplication of 43 kb was identified in nine NCMD families (with evidence for a shared ancestral haplotype), and another one of 45 kb was found in a single family. The MCDR3 locus is thus refined to a shared region of 39 kb that contains DNAse hypersensitive sites active at a restricted time window during retinal development. Publicly available data confirmed expression of IRX1 and ADAMTS16 in human fetal retina, with IRX1 preferentially expressed in fetal macula. These findings represent a major advance in our understanding of the molecular genetics of NCMD at the MCDR3 locus and provide insights into the genetic pathways involved in human macular development.\n\nAbbreviations list

genomics↗